Insecticides

ABSTRACT

WHERE Q represents halogen or hydroxy, R1 and R2 represent hydrogen or alkyl and R3 represents aryl, useful as intermediates in the preparation of insecticidal cyclopentenoneyl chrysanthemates and analogues thereof, are prepared by halogenating the cyclopentenone where Q H and, if desired converting the halogen to hydroxy. Cyclopentenones of the general formula

Unite States atent 1191 Elliott et al. Jan. 7, 1975 [54] INSECTICIDES2,768,965 10/1956 S tansbury et al. 260/468 H [75] Inventors: MichaelElhott, Harpenden; Norman Primary Examiner Daniel D. Horwitz FrankJanes, Luton, both of Attorney, Agent, or Firm-Cushman, Darby & Englandv Cushman [73] Assignee: National Research Development Corporation,London, England [57] ABSTRACT [22] Filed: July 11, 1972 Cyclopentenonesof the general formula [21] Appl. No.1 270,635 g i Related US.Application Data -01rmi [62] Division or Ser. No. 52,084, July 2, 1970,Pat. NO. 11

where Q represents halogen or hydroxy, R and R 52 US. c1. 260/590represent hydrogen or alkyl and 3 represents aryl, 51 1111.01. C07C47/80 useful as intermediates in the Preparation of inseeti- [58] Fieldin Search 260/590, 468 H eidal eyelepenteneneyl ehrysanthemares andlogues thereof, are prepared by halogenating the cy- [5 R f r n it dclopentenone where Q H-and, if desired conyerting UNITED STATES PATENTSthe halogen hYdYOXY- 2,603,652 7/1952 Schechter et al. 260/468 H 2Claims, No Drawings INSECTICIDES This is a division of application Ser.No. 52084, now US. Pat. No. 3,720,703 filed July 2, 1970.

This invention'relates-to insecticides and more particularly tosynthetic insecticides of the pyrethroid class and to their preparationand to compositions containing them.

For many years, research has been pursued in the field of syntheticanalogues of the pyrethrins in order to discover synthetic substituteshaving properties superior to those of the natural products.Insecticidal toxicity and knock-down are important but also importantare low toxicity to mammals and lack of persistence of toxic residues tocontaminate the environment. Ideally, synthetic analogues of thepyrethrins should compare well with the natural products as regardslevel of toxicity to insects and mammals, insecticidal spectrum, andknock-down properties, and in addition should offer ease of manufacture.Very few synthetic compounds have fulfilled all these requirements andfewerstill have shown an improvement over the natural pyrethrins inbiological properties whilst at the same time being simple to prepare. I

The pyrethrins are esters of certain substituted cyclopropane carboxylicacids and substituted cyclopentenolones, and in many syntheticanalogues, that part of the ester which derives from the alcohol hasbeen modified. Thus, analogues have been prepared from cyclopentenolonescontaining substituents at. the 2- position which are different fromthose present in the natural products. Important advances have also beenmade with the use of entirely different alcohols derived, for example,from the aromatic and heterocyclic series. Most modifications of thecyclopentenolone ring have been restricted to varying the nature of the2- substituent but the 3-methyl group present in the natural productshas invariably been retained in the synthetic analogues prepared.

It has now been found that substituted cyclopentenolones which have nomethyl group at position 3 give rise to esters which compare well and,in some cases, surpass pyrethrins in at least one of the desiredproperties whilst being, for the most part, relatively easy to prepare.

Accordingly, the present invention provides compounds of the generalformula:

wherein X, represents a halogen, alkenyl or aryl group,

X X and X which may be the same or different,

each represents hydrogen or a halogeno, alkyl or aryl group, R and Rwhich may be the same or different,

each represent hydrogen or an alkyl group and R represents an organicradical having carbon to carbon unsaturation in a position a to the CHgroup to which R is bonded.

When alkyl, alkenyl, alkynyl or alkoxy substituents .are presentincompounds of the invention, it is preferred that they contain not morethan 6 and more preferably not more than four carbon atoms and theprefix lower, when used, indicates this preferred carbon atoms content.The terms alkyl, alkenyl etc. include cyclo-alkyl, cyclo-alkcnyl etc.and sites of unsaturation in cyclic groups may be endocyclicorexocyclic.

The new pyrethroids according to the present invention are formallyderivable from alcohols of general formula I:

wherein R R and R are as defined above.

However, it is, in practice, less convenient to prepare the esters by anesterification reaction than to proceed by way of the correspondinghalogeno derivative of general formula II:

wherein R R and R are as defined above and X is a halogeno group,preferably bromine or chlorine. In-

deed, proceeding through the halogeno derivative is especiallyconvenient in that the halogeno compound need not be isolated from thereaction medium in which it is produced but can be immediately convertedinto the appropriate ester by reaction with a functional derivative ofthe desired acid, e.g. a suitable salt thereof such as a silver salt oran amine salt, e.g. a triethylamine salt. The compound of formula IIcan, if desired, be converted to the alcohol of formula I by reactionwith silver acetate and hydrolysis'of the acetate of the alcohol withalkali.

The alcohols and corresponding halogeno compounds illustrated above areincluded in the scope of the present invention. Examples of compoundswhich may be used in the present invention are those in which R, and Rare selected from hydrogen, methyl or ethyl, and R represents arylincluding phenyl and substituted phenyl containing halogeno, loweralkyl, lower alkoxy substituents, e.g. telyl, xylyl, p-chlorophenyl,pmethoxyphenyl. R may also represent 2- or 3- furyl. R may alternativelyrepresent an alkenyl group such a vinyl or prop-l-enyl orbut-1,3-dien'yl. i

The insecticidal esters of the present invention are derivable compoundsfrom the substituted cyclopropane carboxylic acid I CO I Y 01 wherein XX X and X, are as definedabove and specific examples of carboxylic acidswhich may be converted into the esters of this invention are:

Chrysanthemic andpyrethric acids (X isobutenyl orZ-methoxycarbonyl-prop-l-eriyl respectively, X H, X X, CH including the(i)-cis-trans, (i)- trans, (i)-cis, (+)-trans and (+)-cis isomersthereof, the isomers of2,2-dimethyl-3-(cyclopentylidenemethyl)-cyclopropane carboxylic acid,2,2-dimethyl, 2,3- dimethyl, 2,3,3-trimethyl, 2,2,3,3-tetramethyl,2,2,3,3- tetraethyl, 2,2-dichloro-3,3-dimethyl, dimethyldiethyl,trimethylethyl, 2,2-dimethyl-3-phenyl, trimethylphenyl anddimethylethylphenyl cyclopropane carboxylic acids. Acids of particularimportance are for example 2,2-dimethyl, 2,3-dimethyl, 2,3,3-trimethyl,2,2- dichloro-3,3-dimethyl and 2,2-dimethyl-3-phenyl.

III

The esters of the present invention can be prepared by conventionalesterification methods, that is to say by reacting a cyclopentenolone offormula IV with an acid or derivative thereof of formula V:

where R R R X X X and X, are as defined above and P and Q are functionalgroups which will react together to form an ester linkage. As mentionedabove, it has been found convenient in practice to react a halogenocompound (Q halogen) with a salt of the carboxylic' acid (P O*M where Mis preferably a silver or triethylammonium cation) but other knownesterification techniques may also be used.

CHzRg The 2-ene of formula VI isa known compound where R and R arehydrogen and R is phenyl (2-benzylcyclo-pent-Z-enone). In general,compounds of formula V1 may be prepared by a condensation reactionbetween cyclopentanone and the aldehyde R CHO followed by anintramolecular rearrangement to produce the'Z-ene as described in theliterature (Conia & Amice,.Bull. Soc. Chim. France 1968 P 3327).

Where one or both of R and R are other than hydrogen these radicals maybe introduced by alkylation at ver trans chrysanthemate (6.1 g.) for 4hours.

After cooling, the mixture is filtered, solvent removedby distillation,and the residue in benzene passed through a column of alumina g.).Distillation of the eluate gives -l.7 g. of a fraction having b.p. n1.5400, shown to be 2-benzylcyclopent-2-enon-4-yl trans chrysanthemate.

EXAMPLE 2 2-Benzylcyclopent-2-enone (5.4 g.), N- bromsuccinimide (5.5g.) and carbon tetrachloride (40 ml) are refluxed for 2 hours, cooled,filtered, treated with silver 2,2,3,3-tetramethylcyclopropanecarboxylate (6.9 g.) and refluxed for 4 hours. After cooling, themixture is filtered, solvent removed by distillation, and

. the residue in benzene passed through a column of alumina (5 g.),Distillation of the eluate gives 1.5 g. of a fraction having b.p.160/0.01 mm, n 1.5330, shown to be 2-benzylcyclopent-2-enone-4-yl2,2,3,3- tetramethylcyclopropane ,carboxylate.

EXAMPLE 3 I v 2-Benzylcyclopent-2-enone (5.0 g.), N-

bromsuccini'mide (5.15 g.) and carbon tetrachloride (40 ml) arerefluxedfor 2 hours, cooled, filtered,

- treated with silver (i)-2,2-dimethylcyclopropane carthe 5-positioneither of the 2-ene or of its immediate precursor.

' compositions.

The insecticidal compositions described above may be used for killinginsects on a domestic or agricultural scale by treating the insectsthemselves where insectinfestation has already taken place or bytreating an environment susceptible to insect attack with thecomposition as a preventive measure.

The invention is illustrated in the following Examples (Temperatures arein C).

EXAMPLE 1 '2-Benzylcyclopent-2-enone (4 g.), N-

bromsuccinimide (4 g.) and carbon tetrachloride (15 ml.) with a trace ofdry be nzoyl peroxide are refluxed for 1% hours, filtered, and thefiltrate refluxedwith si1-' "4-yl-(i) -2,2 dimethylcyclopropane'carboxylate, b.p.

153l60/0.02 min, n 1.5400.

EXAMPLE 4 a. A mixture of cyclopentanone (19.2 g.) andpchlor'obenzaldehyde (10.55- g.) is added dropwise during 1% hours to asolution of sodium hydroxide'(4.'0 g.) in water (150 ml), then stirredat 20 for 4 hours, and neutralised with concentrated hydrochloric acid.The reaction mixture is then extracted with ether, and the extractwashed with aqueous sodium carbonate, saturated sodium chloride, driedover sodium sulphate and distilled to give a fraction, b.p. 163-165 /0.lmm in 30% yield. This was recrystallised frompentane to give -2-(p-chlorobenzylidene) cyclopentanone m.p. 7880. Thisflis a new compound.

2-(p-Chlorobenzylidene) cyclopentanone (48.6 g.) in boilingmethoxy-ethanol (500 ml) is treated dropwise with methoxy-ethanol (50ml) saturated with dry hydrogen chloride gas during 1 hour, then boiledfor 2 hoursQDistillation gives 2-(p-chlorobenzyl) cyclopent- 2-enonewhich is a new compound, b.p. l06/0.l

mm., n 1.5698 in 50% yield.

b. 2-(p-chlorobenzyl) cyclopent-2-enone (4.14 g.) and N-bromsuccinimide(3.56 g.) in carbon tetrachloride (35 ml) is boiled for. 2 hours,cooled, filtered,

EXAMPLE 5 a. A mixture of cyclopentanone (101 g.) andpmethylbenzaldehyde (72 g.) is added to sodium hydroxide (30 g.) inwater (1.2 1.) during 1 hour at 20.

Stirring is continued for 2% hours, then concentrated hydrochloric acidadded until mixture is neutral. The

mixture is extracted with ether and the ether extract washed and driedas described in, Example 4 and distilled to give2-(p-methylbenzylidene)cyclopentanone, m.p. 63-68. I

This product (39 g.) is rearranged on treatment with hydrogen chloridein hotmethoxy-ethanol as described in Example 4 to giveZ-(p-methylbenzyl) cyclopent-2- cnonc which is a new compound, b.p.899l/lmm, n 1.5520, (13 g. 33% yield).

b. Z-(p-Methylbenzyl) cyclopent-Z-enone (3.72 g.) and N-bromsuccinimide(3.56 g.) in carbon tetrachloride (35 ml) is refluxed for 1 /2 hours,cooled, filtered and boiled with silver (+)-trans'chrysanthemate (5.5g.) for 6 hours, cooled, filtered and distilled. The product (.l.0'g.),Z-(p-methylbenzyl) cyclopent-2-enone- 4-yl trans chrysanthemate, boilingat 176-194/0.01 mm, n 1.5395.

The esters of the present invention may be incorporated as activeingredient in insecticidal compositions and the following Examples aregiven'to illustrate typical formulations.

. EXAMPLE 6 Oil-based liquid spray for household insects active compound0.015% w/v 25% Pyrethrum Extract 0.25% Piperonyl butoxide 0.5%Antioxidant, e.g. Topanol A" 0.1% Odourless light voil solvent,

e.g. xylene to make 100 vols.

EXAMPLE 7 Water-based liquid spray concentrate for mosquito controlactive compound 0.25% w/v 4O Piperonyl butoxide 1.0%

Non-ionic emulsifier, e.g. Ethylan BCP" 0.25% Antioxidant, e.g. TopanolA 0.1% Water to make 100 vols.

This concentrate should be diluted 1:80 v/v with water before spraying.

Antioxidant, e.g. Topanol A" EXAMPLE 9 Mosquito coil active compound0.25% w/w Tabu powder or Staragel No. 1. 30.0%

Filler(s), e.g. wood flour, powdered 68.75% leaves or nut shellsBrilliant Green 0.5% p-Nitrophenol 0.5%

EXAMPLE 10 Emulsifiable concentrate active compound 15% w/w Non-ionicemulsifier, e.g. .Ethylan BCP 25.0% Xylene 73.4% Antioxidant, e.g."Topanol A 0.1%

This concentrate may then be diluted atthe rate of 30 mls. to 4% litresof water prior to use.

. EXAMPLE 11 General purpose powder for household, garden, livestock orgrain storage use active compound 0.05% w/w Tropital 0.25% Antioxidant,e.g. butyl hydroxy toluene or butyl hydroxy anisole 0.03% Filler, e.g.Talc BPC 99.67%

In contact toxicity tests, the toxicity of compounds against house flies(adult female Musea domestica L) and mustard beetles (adult Phaedoncochlearae Fab.) was determined by applying a measured volume of anacetone solution containing a known weight of compound to the insect. AnLD value, the weight of compound required to kill 50% of the insects ina statistically significant sample was calculated and comparison of LDvalues obtained under comparable conditions enables relative toxicity tobe determined. In these tests, a relative toxicity of was assigned to5-benzyl-3-furylmethyl (+)cis-transchrysanthemate, a

compound having an extremely high toxicity towards house flies andmustard beetles and which had, under conditions of the present test, LDvalues of 0.01 micrograms per insect towards mustard beetles and 0.012micrograms per insect towards house flies. To determine the effect ofthe .synergist Sesamex (the 2-(2- ethoxyethoxy)-ethyl-3,4-methylenedioxyphenyl acetal of acetaldehyde), on the synthetic pyrethrins, 2micrograms of Sesamex were applied to each test insect 2 hours beforeapplication of insecticide. LD values were then calculated as before anda synergistic factor calculated by comparing LD values with and withoutsynergist. The knock-down effect of the insecticides was tested bydetermining the time taken for 50% of a sample of insects to be-knocked-down under the influence of the insecticide under test. Thefollowing results were obtained.

Synergistic factor Test Compound Relative Toxicity Knockdown MustardBeetles House Flies (house flies) (house flies)2-benzylcyclopent-2-enone 4-yl I (+)-trans-chrysanthernate 46 23 50-100high Z-benzylcyclopent-2-enone-4-yl 2,2,3,3-tetramethyl cyclopropane f41 air carboxylate 4.5

Test Compound Continued Relative Toxicity Synergistic factor Knock-downMustard Beetles House Flies (house flies) (house flies)2-benzylcyclopent2-enone-4-yl (:)-2,2-dimethyl cyclopropane carboxylatel low 2-(p-chlorobenzyl)-cyclopent 2-enone-4-yl (+)-trans-chrysanthemate4.8 7

2(p-methylbenzyl)-cyclopent-2-enone-4-yl (+)-trans-chrysanthemate l5 l6S-benzyl-3-furylmethyl (+)-transchrysanthemate 270 240 7 low5-benzyl-3-furylmethyl (:)-cis. trans-chrysanthemate I00 100 12 lowZ-benzyl-3-methyl-cyclopent-2-enone-4-yl (i)-cis-trans-chrysanthemate5.5 1.9 natural pyrethrins 36 6 200 high We claim: 7 l. Cyclopentenonesof the general formula;

R2 I I wherein Q represents aibromo. group R and R which may be the sameor different, each represent hydrogen or an alkyl group containing one.to six carbon atoms methylbenzyl)-4-bromo-cyclopent-Z-enone.

Patent: No. 3 Dated January 7, 1975 I .w.MiQhQQL .E ll .i O angi NormanFrank James Page 1 of 2 It is ccrt'iz'fw'od that error appears in theahovcddentificzl patent and that said Letters Patent; are herebycorrected as shown below:

In the heading insert Claims priority British Application No. 34787/69filed July 10, l969.

Column 2 ,line 41 change "telyl" to .tolyl-.

Column 2 line 57 change "X3=X4 CH to X3=X4=CH Column 4, line 1 change,trans" to trans.

UNE'EZCEE FYfUxi-YEQ P/Jiliiii QFFEC E N [f\ F "'1' Y I: 71' I'I I EX-(15R .21 ll. E Q1 C(Jirmrbw l; 4- ll? LO 335.94135l7r.. w. i-l --llannar;/; 7 l91i Page 2 of 2 Inventor(s) biichael E l l 1ott and NormanFrank James It is certified that: error appears in the above-identifiedpaLc-nt e and that said Letters Patent are hereby corrected as shownbelow: I

Please add the following claim;

3. Cyclopentenones according to Claim 1 wherein O R and R each representhydrogen.-

Signed and Sealed this 0 eleventh a' [SEAL] D y Of May 1976 Arrest:

:13 C. (IyA SON c. MARSHALL DANN (mnmissimn'rnj'l u-m Trademarks

1. CYCLOPENTENONES OF THE GENERAL FORMULA:
 2. A compound according toclaim 1 which is 2-benzyl-4-bromo-cyclopent-2-enone,2-(p-chlorobenzyl)-4-bromo-cyclopent-2-enone or2-(p-methylbenzyl)-4-bromo-cyclopent-2-enone.